The use of transdermal patches for time-released drug delivery is well known in the medical community. Transdermal patches are used to deliver a wide variety of pharmaceuticals including estrogen, nicotine, lidocaine and other molecules that are able to pass through the skin (see, e.g., U.S. Pat. Nos. 5,965,154, 5,972,377, 6,207,182, and the like). The controlled release of drugs offers advantages over oral and/or injected medications in terms of convenience and more importantly, the maintenance of a steady therapeutic concentration of medicament.
Oral doses of lithium salts including lithium carbonate and lithium citrate are well known for the treatment of bipolar disorder. Unfortunately the blood concentration of lithium ion (Li+) changes rather sharply over time after ingestion of the lithium salt. The typical blood volume for a human is about 5 liters. According to the National Institute of Health (NIH) (see, e.g., website://dailymed.nlm.nih.gov/dailymed/about.cfm), the target value for treatment of bipolar disorder is approximately 0.6 to 1.2 mEq/l. Given a total blood volume of 5 liters, the total lithium dosage for treatment of biopolar disorder is about 3 to 6 mEq which translates to 21 to 42 milligrams of lithium (metal). Assuming an average uptake of 30 mg Li+ every 12 hours (60 mg/day), a lithium patch supplying Li+ for one week (14 doses) would need 420 mg of lithium metal (less than half a gram). If the lithium source were a lithium carbonate salt (mol wt.=73.89), one would need 111 to 222 mg of Li2CO3 to achieve the therapeutic concentration of 3 to 6 mEq, respectively. So a one-week lithium patch having a Li2CO3 salt as the source of lithium would require at least 1554 to 3108 mg of salt.
When taken orally, a typical dosage is around 300 mg of Li2CO3 to achieve the therapeutic target of 3 to 6 mEq of Li+. Unfortunately, the therapeutic value for lithium is very close to the toxic threshold, and there is no known antidote for lithium poisoning.
The idea for a lithium transdermal patch is described in Raimondi (U.S. Pat. No. 6,207,182), where a simple adhesive patch containing a lithium salt is used for delivery of lithium. There are problems with this approach, notably the large amount (volume) of lithium salt necessary for treatment of bipolar disorder, leading to a cumbersome patch. Also, using the simple patch in Raimondi lithium uptake rates may not be sufficient to provide effective treatment.
The use of iontophoresis for transdermal lithium delivery is described by Nemeroff et al. (U.S. Pat. No. 6,375,990). However, this device suffers from the same problem as the adhesive patch described by Raimondi (supra.) in that a large reservoir of lithium salt is needed, and in direct contact with skin, leading to a cumbersome patch that limits the duration of drug delivery related to practical volume restrictions. Moreover, these devices do not have control over the rate and/or quantity of Li delivered. These devices also require the use of an external battery, which further complicates their design and use.